COVID-19 and Treatment

Given the current lack of a vaccine, the seriousness of the COVID19 pandemic and its capacity to cause death in older patients, clinicians and scientists are assessing whether there are any drugs in the global pharmacopoeia that can be re-purposed to mitigate symptoms, reduce the time to recovery and/or fend off death from this infection.

So far, we have not had time to specifically develop anything new, either to stop the virus replicating or to suppress the inflammatory response that develops with the disease. Therefore, we look to what we already have, and use what we can, based on our understanding of the COVID19 disease process or the related viral infections MERS and SARS.

Before moving to describe possible treatments, it is worth providing a little detail of the infectious process, as this will illuminate possible intervention points.

The infection process

The first intervention point is at the point of virus entry. Initially, the virus is inhaled and binds to the surface of the respiratory epithelium via specific receptors, allowing it to gain entry to the cell and propagate. Patients are usually asymptomatic at this point (stage 1) but may shed the virus and become infectious.

The next intervention point occurs when the virus migrates down the upper airways stimulating a vigorous innate immune response which, in most infected patients, is likely to be sufficient to limit the spread of virus resulting in a relatively mild disease (stage 2).

However, in about 20 percent of patients, the virus migrates to the lower lung and infects cells involved in gas exchange, representing the third potential intervention point.

Here, large amounts of virus are produced and many of these lung cells die, leading to the reduced oxygenation of blood (stage 3). This stage is also associated with the release of molecules that cause significant and damaging inflammatory responses.

Treatment options

An effective vaccine would be the ‘gold standard’ form of (preventative) treatment since it limits virus entry (and the development of subsequent stages) by stimulating the body to produce virus-specific antibodies that would help destroy the virus.

Whilst we anxiously await vaccine development, we cannot afford to ignore other means of dealing with the disease, both physical and chemical. With regard to the physical, relatively simple measures, such as the wearing of masks and practising social distancing have been introduced, both purposed to restrict entry of the virus into the lungs. With regard to chemical measures, you have probably heard mention of several, including hydroxychloroquine, dexamethasone and Remdesivir. Of these, evidence indicates that hydroxychloroquine and dexamethasone may have benefit in treating hospitalised COVID19 patients.

Hydroxychloroquine

Hydroxychloroquine was introduced in 1955 to treat malaria, and this and similar drugs were found accidentally to improve the health of people with a variety of autoimmune diseases. Subsequently, these drugs were also shown to possess a number of antimicrobial effects including the inhibition of COVID19 and HIV virus replication in the test tube. These findings have stimulated researchers to determine whether they might be useful in treating both stage 2 and 3 COVID19 disease, despite not knowing precisely how they work. The results from a number of COVID19 studies have been variable but at least recent study in the US showed that in a large group of hospitalised patients treated with drug, a significant reduction in COVID19 mortality was observed compared with patients who were not treated.

Dexamethasone

Dexamethasone has been shown to help COVID19 patients having difficulty in breathing due to the infection but not in those without this problem. It is likely to work by suppressing the severe inflammation induced by the virus in the later stages of disease.

Remdesivir

Remdesivir targets the viral replication process in stage 2 of the infection but results so far, in a hospital setting, indicate only marginal improvement over placebo.

From the above, it can be seen that much work is being done to help patients with COVID19 and many trials of these drugs and other candidates are underway given the enormity of the problem. We must await the results from the many other ongoing trials with these and other drugs with patience.